Subunit composition determines picrotoxin and bicuculline sensitivity of Drosophila gamma-aminobutyric acid receptors.
Subunit composition determines picrotoxin and bicuculline sensitivity of Drosophila gamma-aminobutyric acid receptors.
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发表时间：
1995-11
影响因子：
3.6
通讯作者：
H. G. Zhang;H. Lee;T. Rocheleau;R. ffrench-Constant;M. Jackson
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文献类型：
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作者：
H. G. Zhang;H. Lee;T. Rocheleau;R. ffrench-Constant;M. Jackson
从昆虫中克隆到的γ -氨基丁酸（GABA）受体亚基很少。这些包括对狄氏剂（Rdl）的抗性，以及脊椎动物GABAA受体β亚基的同源物。与大多数脊椎动物GABAA受体亚基不同，Rdl形成了一种高功能的同质受体。该受体对微毒素（PTX）敏感，但对双核碱（BIC）不敏感，无法在已知的GABAA受体亚型中轻易分类。相比之下，β亚基同源物的功能表达尚未报道。我们报道了含有Rdl和β亚基的重组杆状病毒的细胞共感染诱导具有不同药理学和动力学特性的GABA受体。共感染产生两种不同的受体群体：一种对PTX高度敏感，但BIC不敏感（Rdl同聚体），另一种PTX不敏感，BIC敏感（Rdl + β异聚体）。假设的Rdl + β通道也表现出GABA敏感性降低、脱敏缓慢、破裂迅速和平均打开时间缩短。这些研究不仅定位了PTX和BIC对两种不同GABA受体亚基的敏感性，而且证明了两种高度不同的GABA受体亚基的组装。此外，体内通道和重组通道之间的通道电导和门控差异表明果蝇中存在未表征的GABA受体亚基。
Few gamma-aminobutyric acid (GABA) receptor subunits have been cloned from insects. These include Resistance to dieldrin, or Rdl, and a homologue of the vertebrate GABAA receptor beta subunit. Unlike most vertebrate GABAA receptor subunits, Rdl forms a highly functional homomultimeric receptor. This receptor is picrotoxin (PTX) sensitive but bicuculline (BIC) insensitive and cannot be readily classified within the known GABAA receptor subtypes. In contrast, functional expression of the beta subunit homologue has not been reported. We report that coinfection of cells with recombinant baculoviruses containing Rdl plus beta subunits induces GABA receptors with distinct pharmacological and kinetic properties. Coinfection produces two separate receptor populations: one highly sensitive to PTX but BIC insensitive (Rdl homomultimers) and the other PTX insensitive and BIC sensitive (Rdl plus beta heteromultimers). Putative Rdl plus beta channels also show reduced GABA sensitivity, slow desensitization, rapid bursting, and shorter mean open time. These studies not only localize PTX and BIC sensitivity to two distinct GABA receptor subunits but also demonstrate assembly of two highly divergent GABA receptor subunits. Furthermore, the difference in channel conductance and gating between in vivo and recombinant channels implies the existence of uncharacterized GABA receptor subunits in Drosophila.